Inhibition of nitric oxide synthesis by interleukin-4 may involve inhibiting the activation of protein kinase C epsilon

Sands, W. A., Bulut, V., Severn, A., Xu, D. and Liew, F. Y. (1994) Inhibition of nitric oxide synthesis by interleukin-4 may involve inhibiting the activation of protein kinase C epsilon. European Journal of Immunology, 24(10), pp. 2345-2350. (doi: 10.1002/eji.1830241013) (PMID:7523136)

Abstract

The murine macrophage cell line, J774, when activated with interferon-γ (IFN-γ), expressed high level of inducible nitric oxide synthase (iNOS) and bound significantly more [3H]-phorbol-dibutyrate (PBu2) compared to non-activated cells. The increased PBu2 binding to the particulate fraction of the cells is a measure of activation and translocation of protein kinase C (PKC). Both the expression of iNOS and the enhanced PBu2 binding in the activated J774 cells were significantly inhibited by the pretreatment of the cells with murine recombinant interleukin-4 (IL-4). Stimulation of J774 cells by IFN-γ and lipopolysaccharide results in the translocation predominantly of the epsilon isoform of PKC (PKC-ϵ), and this is inhibited by IL-4. The inhibition of PKC activation was also evident by measuring the PKC activity in the cytosolic fraction of the IL-4-treated cells. Activated J774 cells pretreated with IL-4 or a PKC-specific inhibitor (RO31-8220) failed to express mRNA of iNOS analyzed by PCR. These results, therefore, suggest that the inhibition of nitric oxide synthesis in activated murine macrophages by IL-4 is at the transcriptional level and may involve the inhibition of the activation of PKC-ϵ.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liew, Prof Foo and Xu, Dr Damo and Sands, Dr William
• Authors: Sands, W. A., Bulut, V., Severn, A., Xu, D., and Liew, F. Y.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: European Journal of Immunology
• Publisher: Wiley-VCH Verlag
• ISSN: 0014-2980
• ISSN (Online): 1521-4141